Posted on February 23, 2024

It is not recommended to train for a trail half-marathon on flat land, and tell yourself that just running 18-20 miles will be fine. Altitude and gravity don't work that way. Anywho...

It is ubiquitously understood that regular cardiovascular exercise contributes to longevity and improves physical health. But does it do anything for our brains? Ongoing research has explored this question for decades, and experts echo a resounding yes. Exercise sharpens our minds, lifts our mood, and protects our brain cells from damage that occurs as we age. These remarkable results are thanks to a powerful protein called brain-derived neurotrophic factor (BDNF).

What is BDNF?

BDNF is a member of a group of proteins known as neurotrophins, which are important for the development, growth, and maintenance of neurons. BDNF is secreted throughout the body by platelets, skeletal muscle, and other organs, but it is most densely concentrated in the brain.[1]

BDNF in Learning, Memory, and Cognition

BDNF is involved in the intriguing phenomenon known as neuroplasticity, or the ability for the brain to evolve with our experiences. These changes stem from strengthening or weakening connections between neurons within key pathways for differing functions. An important pathway for learning and memory begins in an area located deep inside the brain called the hippocampus. The initial events necessary for encoding and storing new information originate in this structure, so a substantial degree of neuroplasticity, or the ability for the brain to change with outside circumstances, here is essential. 

It is not surprising that the highest amounts of BDNF are found in the hippocampus.[1] The canonical, or supreme master, receptor for BDNF is called TrkB, and when they interact, a cascade of molecular signals play a game of Telephone, telling the end receiver to trigger essential changes that strengthen connections between neurons in this pathway. 

With perfect synchronicity, BDNF sets off other molecular pathways that further strengthen these same connections, orchestrating the formation of a robust memory or learning experience. This is a fancy way with a lot of words to say "lasting memory [1]."

BDNF has the added benefit of enhancing neuroplasticity in areas of the brain important for cognition, or higher thinking, critical thinking, problem solving, and decision-making. The effects of BDNF don’t stop here! Nay! BDNF and its effects are also set up to combat the cognitive deterioration that occurs with age. Dementia and its associated symptoms. The things you do not want. 

In addition to its effects on neuroplasticity, it is a tireless warrior that promotes the proliferation and survival of brain cells, boosts pro-immunity effects (much research on the inmmune system and silent inflammation and aging), drives tissue repair, and acts as a potent antioxidant, scavenging those pesky nasty things you take vitamins to avoid ravaging your body [2]. 

BDNF has even been proposed as a therapeutic for Alzheimer’s disease, as animal models have shown that BDNF can facilitate communication between neurons in diseased mice to restore learning and memory [3].

BDNF and Depression

BDNF also modulates our emotional landscape, as the hippocampus is an important area of focus for the treatment of anxiety and depression. In one study, serum and plasma levels (the runny stuff your red blood cells flow around in) were significantly lower in clinically depressed patients as compared to controls [4]. It was suggested that less BDNF was being secreted within key areas in the brain associated with depression, mainly the hippocampus [5]. 

A multitude of mechanisms have been proposed to explain why this occurs, and one leading theory is that a mutation in the BDNF gene or its receptor is the cause for decreased levels of BDNF and low mood [6].

What Happens if You Have Reduced Levels of BDNF?

Animal studies show that blocking the action of BDNF impairs neuroplasticity, causing defects in learning and memory [7], and behavioral signs of depression [6]. These deleterious effects are reflected in humans with reduced BDNF levels, such as patients with depression [4], stroke [8], and Huntington’s disease [9].

Most relevant to the scope of this article, BDNF is intimately related to lifestyle choices and exercise.

Low levels of BDNF are associated with cognitive deficits in patients with type II diabetes, especially in those with unhealthy eating habits and sedentary lifestyles [10]. 

How do You Increase BDNF?

Although some B vitamins can boost BDNF to some degree, exercise is the most effective way to elevate its levels to keep your mind sharp and your spirits high. Importantly, the type of exercise that you do matters. A 2022 meta-analysis of 21 randomized, controlled clinical trials with 809 participants demonstrated that exercise increased BDNF levels in men and women performing both acute and long-term aerobic exercise. The intensity of aerobics did not seem to make a difference, but traditional strength training alone had no effect [2].

This is because breaking a good sweat and keeping the heart pumping improves the function of blood vessels, insulin balance, metabolism, and blood flow to the brain which all stimulate BDNF release from the brain, muscles, platelets, and other areas. Interestingly, though everyone benefited from exercise, the effect was more pronounced in women over the age of 60 [11, 12]. Sorry, guys.

Conclusion

The bottom line is that making regular exercise a priority is one of the best ways to enjoy life-long health and wellness. Some of the multitude of physical benefits include strengthening the cardiovascular system, balancing insulin levels, increasing bone density, maintaining muscle mass, and an overall feeling of well-being. 

Exercise also improves and protects the most important organ in the body: the brain. Establishing a lifetime aerobic exercise routine isn’t just for looking good in your clothes. It’s essential for promoting mental health and preserving a keen mind.

I have no comment on my decision on half-marathon training.

References

1. Loprinzi, P.D. and E. Frith, A brief primer on the mediational role of BDNF in the exercise-memory link. Clin Physiol Funct Imaging, 2019. 39(1): p. 9-14.

2. Wang, Y.H., et al., The effect of physical exercise on circulating brain-derived neurotrophic factor in healthy subjects: A meta-analysis of randomized controlled trials. Brain Behav, 2022. 12(4): p. e2544.

3. Nagahara, A.H., et al., Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med, 2009. 15(3): p. 331-7.

4. Karege, F., et al., Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.Biol Psychiatry, 2005. 57(9): p. 1068-72.

5. Paredes, D.A., et al., Bdnf deficiency in the neonatal hippocampus contributes to global dna hypomethylation and adult behavioral changes. Brain Res, 2021. 1754: p. 147254.

6. Martinowich, K., H. Manji, and B. Lu, New insights into BDNF function in depression and anxiety. Nat Neurosci, 2007. 10(9): p. 1089-93.

7. Vaynman, S., Z. Ying, and F. Gomez-Pinilla, Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition.Eur J Neurosci, 2004. 20(10): p. 2580-90.

8. Karantali, E., et al., Serum BDNF Levels in Acute Stroke: A Systematic Review and Meta-Analysis. Medicina (Kaunas), 2021. 57(3).

9. Ciammola, A., et al., Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients.Am J Med Genet B Neuropsychiatr Genet, 2007. 144B(4): p. 574-7.

10. Zhen, Y.F., et al., Low BDNF is associated with cognitive deficits in patients with type 2 diabetes. Psychopharmacology (Berl), 2013. 227(1): p. 93-100.

11. Lemos, J.R., Jr., et al., Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism. Physiol Genomics, 2016. 48(2): p. 116-23.

12. Zembron-Lacny, A., et al., Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men.Braz J Med Biol Res, 2016. 49(7).